The enhancement of autophagic flux induced by oxaliplatin in hepatocarcinoma cell line HepG2 and its influence on cell proliferation / 肿瘤

ABSTRACT

Objective: To investigate the change in function of autophagy in hepatocarcinoma cell line HepG2 induced by Oxa (oxaliplatin), and to explore the role of autophagy in Oxa-induced cell death. Methods: The HepG2 cells were routinely cultured in vitro and treated either with different concentrations of Oxa alone or in combination with the autophagy inhibitor 3-MA (3-methyladenine ) or CQ (chloroquine). The cell viability was detected by CCK-8 (cell counting kit-8) assay. The formation of autophagosomes was observed directly under TEM (transmission electron microscope). Western-blotting was used to track the conversion of autophagic marker proteins LC3-I to LC3-II. Results: CCK-8 assay demonstrated that Oxa could dose-dependently induce the death of HepG2 cells, and when it was administrated in combination with 3-MA or CQ, Oxa could also significantly inhibit the growth of HepG2 cells. The formation of autophagosomes in HepG2 cells after Oxa treatment could be observed under TEM, as well as an increase in expression of LC3-II was found. The expression of LC3-II increased markedly after the inhibition of degradation pathway induced by CQ, which reflected an enhancement of autophagic flux induced by Oxa. 3-MA could inhibit the formation of autophagosomes in HepG2 cells. Conclusion: Oxa can enhance the function of autophagy in HepG2 cells and induce an increase in autophagosome formation. The autophagy inhibitors 3-MA and CQ can both facilitate the proliferative inhibition of hepatocarcinoma cell line HepG2 induced by Oxa, and they can also increase the antitumor effect of Oxa. Copyright © 2013 by TUMOR.